Association of HER2/neu gene amplification and copy numbers of HER2/neu and chromosome 17 with tumor characteristics in resected colorectal cancer (CRC)

Abstract

3592 Background: HER2/neu is an oncogene on chromosome (chr) 17 that encodes a type I tyrosine kinase growth factor receptor. In breast cancer, HER2/neu status, as assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), reliably identifies aggressive tumors and is routinely used for therapeutic decisions. In CRC, HER2/neu protein overexpression has been studied mostly by IHC, but its significance is still unclear. Our objective was to use FISH to compare various tumor characteristics with HER2/neu gene amplification and copy numbers of HER2/neu and chr 17 as possible markers for aggressive tumors. Methods: HER2/neu gene amplification (defined as a ratio of HER-2/neu to chr 17 centromere of >2), HER2/neu copy number (cutoff >4.37) and chr 17 copy number (cutoff >2.03) were assessed by FISH in 272 surgically resected colon cancers from 02/00 to 04/03. FISH results were correlated with these tumor characteristics: size, grade (1= well, 2=moderately and 3=poorly differentiated) and TNM stage. Statistical analysis was performed using Fisher’s exact test and Student’s t-test. Results: The mean patient age was 67 and 53% were female. Tumor characteristics: mean size, 4.8 cm; median histologic grade, 2 of 3; and most common stage, III (32%), followed by II (30%), I (23%) and IV (15%). HER2/neu gene amplification was detected in 55 of 272 (20%) tumors. The average HER2/neu and chr 17 copy numbers were 2.78 and 1.98, respectively. There was no statistically significant association between HER2/neu gene amplification, HER2/neu copy number or chr 17 copy number when compared to tumor size, grade or stage. Conclusions: Fifty-five out of 272 (20%) CRCs demonstrated HER2/neu gene amplification but no association was found with tumor size, grade or stage. In view of the 20% amplification rate, which approximates that seen in breast cancer, clinical trials with trastuzumab (Herceptin) appear worth pursuing. Correlation of HER2/neu expression with overall survival in these 272 patients is merited. To the best of our knowledge, ours is the largest reported series examining HER2/neu overexpression, HER2/neu and chr 17 copy numbers in CRC by FISH. No significant financial relationships to disclose.